Ana Paula Sakamoto

Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus

BACKGROUND To our knowledge there are no studies assessing anti-Ro/SSA and anti-La/SSB autoantibodies in a large population of childhood-systemic lupus erythematosus (cSLE) patients. METHODS This was a retrospective multicenter cohort study performed in 10 Pediatric Rheumatology services, São Paulo state, Brazil. Anti-Ro/SSA and anti-La/SSB antibodies were measured by enzyme linked immunosorbent assay (ELISA) in 645 cSLE patients. RESULTS Anti-Ro/SSA and anti-La/SSB antibodies were evidenced in 209/645 (32%) and 102/645 (16%) of cSLE patients, respectively. Analysis of cSLE patients with and without anti-Ro/SSA antibodies revealed higher frequencies of malar rash (79% vs. 71%, p=0.032), photosensitivity (73% vs. 65%, p=0.035), cutaneous vasculitis (43% vs. 35%, p=0.046) and musculoskeletal involvement (82% vs. 75%, p=0.046) in spite of long and comparable disease duration in both groups (4.25 vs. 4.58years, p=0.973). Secondary Sjögren syndrome was observed in only five patients with this antibody (2.5% vs. 0%, p=0.0035), two of them with concomitant anti-La/SSB. The presence of associated autoantibodies: anti-Sm (50% vs. 30%, p<0.0001), anti-RNP (39% vs. 21%, p<0.0001) and anti-ribossomal P protein (46% vs. 21%, p=0.002) was also significantly higher in patients with anti-Ro/SAA antibodies. Further evaluation of cSLE patients with the presence of anti-La/SSB antibodies compared to those without these autoantibodies showed that the frequency of alopecia (70% vs. 51%, p=0.0005), anti-Sm (59% vs. 31%, p<0.0001) and anti-RNP (42% vs. 23%, p<0.0001) were significantly higher in the former group. CONCLUSIONS Our large multicenter cohort study provided novel evidence in cSLE that anti-Ro/SSA and/or anti-La/SSB antibodies were associated with mild manifestations, particularly cutaneous and musculoskeletal. Secondary Sjögren syndrome was rarely observed in these patients, in spite of comparable frequencies of anti-Ro/SSA and/or anti-La/SSB reported for adult SLE.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1–23.4) vs 6.2 (0–17) vs 3.3 (0–14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0–9) vs 0 (0–6) vs 0 (0–7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups (p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients:

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304–5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365–5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies (p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

Rituximab use in young adults diagnosed with juvenile idiopathic arthritis unresponsive to conventional treatment: report of 6 cases

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Without an effective therapy, patients may progress quickly to functional disability. Recently, depletion of B cells emerged as a new approach for the treatment of autoimmune diseases, including JIA. We describe six cases of JIA patients followed at a referral center for Rheumatology and Pediatric Rheumatology, submitted to treatment with rituximab (RTX) after refractoriness to three anti-TNF agents. Patients received RTX cycles with two infusions every six months. Response to treatment was assessed by DAS28, HAQ/CHAQ, and an overall assessment by the doctor and the patient. Of our six patients, four were girls (mean age at onset of disease: 6.1 years; mean disease evolution time: 15.1 years; mean age upon receiving RTX: 21.6 years). Four patients belonged to polyarticular subtype (1 rheumatoid factor [RF]-negative, 3 FR-positive), a patient with systemic JIA subtype with a polyarticular course and arthritis related to enthesitis. Of our six patients, five responded to treatment; and during the course of 12 months, the clinical response was maintained, although not sustained. However, discontinuation by infusion reactions caused the withdrawal of RTX in two patients. The use of RTX in JIA is restricted to cases refractory to other biological agents and, even considering that this study was held in a small number of advanced patients, RTX proved to be an effective therapeutic option.

Condrólise de quadril em uma adolescente: evolução clínica e radiológica

Idiopathic chondrolysis of the hip is a rare condition of unknown etiology characterized by progressive destruction of the hyaline cartilage that covers the femoral head and acetabulum. Idiopathic chondrolysis of the hip has an insidious beginning and affects more often female adolescents. Patients report severe hip pain, mobility limitation, and even claudication. This study aimed at reporting one case of that rare disease: an 11-year-old female adolescent with chondrolysis, followed up for three years. Inflammatory activity tests were normal. Imaging tests (radiography, ultrasonography and magnetic resonance) were essential for the diagnosis. The treatment was based on pain control and preservation of the joint mobility, and included low-impact physical activity, non-steroidal anti-inflammatory drugs, and disease-modifying antirheumatic drugs, with good response after 12 months of treatment. Surgery was not necessary.

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus

OBJECTIVES To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. METHODS Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. RESULTS DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p=0.008), discoid rash (16% vs. 4%, p=0.017), photosensitivity (76% vs. 45%, p=0.002) and other cutaneous vasculitides (80% vs. 19%, p<0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p=0.003), fever (32% vs. 56%, p=0.020) and hepatomegaly (4% vs. 23%, p=0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p>0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p=0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p=0.014) was significantly lower in the DV group. CONCLUSION Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2–17) vs. 12 (1.9–17.7) vs. 12.5 (3–18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4–12) vs. 6 (4–13) vs. 6 (4–12), P < 0.0001) and SLEDAI-2 K (18 (6–57) vs. 16 (2–63) vs. 13 (1–49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study

OBJECTIVE To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. METHODS A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. RESULTS At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). CONCLUSIONS Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.

128 Outcomes of 847 childhood-onset systemic lupus erythematousus patients in three age groups

Background and aims To assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease(<6 years), group B school age(≥6and<12 years) and group C adolescent(≥12and<18 years). Methods Observational cohort study of 10 Paediatric Rheumatology centres, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was higher in group A compared to groups B and C[8.3 (0.1–23.4) vs. 6.2 (0–17) vs. 3.3 (0–14.6) years, p<0.0001]. The median SLICC/ACR-DI[0 (0–9) vs. 0 (0–6) vs. 0 (0–7), p=0.065] was comparable in all groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric(21% vs. 10% vs. 7%, p=0.007), skin (10% vs. 1% vs. 3%, p=0.002) and peripheral vascular involvements(5% vs. 3% vs. 0.3%, p=0.008) were more frequent in group A compared to B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia and autoimmune hemolytic anaemia were similar in all groups(p>0.05). Mortality rate was higher in group A compared to groups B and C(15% vs. 10% vs. 6%, p=0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes, with higher mortality rate and neuropsychiatric/vascular/skin organ damages in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

129 Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study

Background and Aims To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus(cSLE) patients with and without panniculitis. Methods Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p<0.004). Results Panniculitis was observed in 6/847 (0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalised distribution was evidenced in 3/6 and localised in upper limbs in 2/6 and face in 1/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75 (0–11.4) vs. 2.83 (0–11.8) years, p=0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p=0.003), leukopenia (67% vs. 7%, p=0.002) and median C-reactive protein (10.5 vs. 0.5 mg/L, p=0.001). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. Conclusions Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.